Abstract
Purpose :
Previous studies have associated autosomal recessive retinitis pigmentosa (RP) 59 to two mutations in the dehydrodolichyl diphosphate synthase (DHDDS) gene, a small gene containing 9 exons positioned at chromosome 1p36.11. Homozygous and compound heterozygous mutations in DHDDS c.124A>G p.(Lys42Glu) are associated with RP. Longitudinal studies characterizing the clinical progression of DHDDS-associated RP is lacking. We analyze the clinical characteristics and natural history of DHDDS-associated RP, with a focus on changes in the ellipsoid zone (EZ) horizontal width as a measure of disease progression.
Methods :
Five individuals (3 female) with a confirmed diagnosis of RP and with confirmed pathogenic mutations in the DHDDS gene were selected from the records of the Division of Ophthalmic Genetics at the Harkness Eye Institute at Columbia University. Comprehensive retinal examination was completed with imaging studies, which include spectral-domain optical coherence tomography (SD-OCT), short-wave autofluorescence (SW-AF), and color fundus photography (Optos 200Tx unit). Measurements of the EZ horizontal width on OCT images taken at initial presentation, year 1 follow up, and year 3 follow up were used to assess disease severity and progression.
Results :
Age at initial visit was ranged from 28 to 69 years old, and best corrected visual acuity ranged from 20/40 to light perception. All patients were homozygous for DHDDS c.124A>G p.(Lys42Glu) pathogenic mutation; all patients were unrelated to each other and are of Ashkenazi Jewish ancestry. Mean EZ horizontal width at first visit was 2279.7 micrometers (sd=2197.7). Log(horizontal EZ width) at first visit was 7.2 (sd=1.4). Fitting linear mixed models, we estimated that average change over time for raw EZ horizontal width was a decline of 151.4 micrometers per year (se=41.5, p-value<0.001). For log transformed EZ width, the average change over time (in years) was a decline of 0.11 (se=0.04, p-values=0.007).
Conclusions :
This study demonstrated a gradual, statistically significant decrease in horizontal EZ width among our patient cohort, highlighting a rapid progression. The rate of EZ width progression is comparable to other genetic mutations causing autosomal recessive RP. Further identification and analysis of patients with DHDDS mutations is needed to better understand disease progression and to establish more effective management strategies.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.